Apparatus for applying a material to small granules

ABSTRACT

The method and apparatus utilize a chamber having a fluidized bed in which a batch of small particles, such as granulated sugar, are suspended. Plural discharge heads are located near the sidewall of the chamber so that they discharge toward the central portion of the chamber. A liquid under pressure is fed through each discharge head and exits therefrom in a stream, the initial portion of which is substantially horizontal and located substantially within a horizontal plane near the upper surface of the bed. Nozzles are connected to a supply of gas under pressure and each one is located substantially directly above a discharge head so that the stream of gas emitted from the nozzle will flow over the discharge end of the discharge head to prevent the accumulation of dried liquid or coated granules thereon. After a specified period of coating, the discharge of liquid is terminated and the batch of coated particles is removed from the bed.

United States Patent Rowe et a1.

Sept. 9, 1975 APPARATUS FOR APPLYING A MATERIAL TO SMALL GRANULES inventors: Englebert L. Rowe, Portage; Gerald [73] Assignee: The Upjohn Company, Kalamazoo,

Mich.

[22] Filed: Nov. 12, 1973 [21} Appl. No.: 414,907

[52] US. Cl. 118/9; 118/24; 118/302;

m yv -fi w: n1 t y. [51] int. C1. B05c 5/00 [58] Field of Search 118/19, 303, 24, 9, DIG. 5, 118/302', 117/D1G. 6, 100 A; 239/292, 295; 264/117 [56] References Cited UNITED STATES PATENTS 3,152,005 10/1964 Tuttlc 118/303 X 3,347,701 10/1967 Yamagishi et a1. 1l8/49.1 X 3,391,003 7/1968 Armstrong et a1.... 264/117 X 3,469,562 9/1969 Grun. 118/303 X 3,518,967 7/1970 Horrocks 118/303 Primary Examiner-John P. McIntosh Attorney, Agent, or Firm-Woodhams, Blanchard and Flynn 5 7 ABSTRACT The method and apparatus utilize a chamber having a fluidized bed in which a batch of small particles, such as granulated sugar, are suspended. Plural discharge heads are located near the sidewall of the chamber so that they discharge toward the central portion of the chamber. A liquid under pressure is fed through each discharge head and exits therefrom in a stream, the initial portion of which is substantially horizontal and located substantially within a horizontal plane near the upper surface of the bed. Nozzles are connected to a supply of gas under pressure and each one is located substantially directly above a discharge head so that the stream of gas emitted from the nozzle will flow over the discharge end of the discharge head to pre vent the accumulation of dried liquid or coated granules thereon. After a specified period of coating, the discharge of liquid is terminated and the batch of coated particles is removed from the bed.

7 Claims, 6 Drawing Figures PATENTEUSEP 9 ms 3, 9 03.8 39

sum 1 or 2 LIQUID GAS PATENTEDSEP" i n I 3,903,839

wmaqz APEARATUS FOR APPLYING A MATERIAL TO SMALL GRANULES BACKGROUND OF THE INVENTION This invention relates in general to apparatus whereby a batch of small particles, such as granulated sugar, can be coated with a liquid containing a binding agent, medication or other excipients and, more particularly, to types thereof wherein the problems previously encountered while using this type of equipment and process are avoided.

The uses for coated or agglomerated granules may be many, but this invention stems from the need for a method of storing, in a dried form, medication which becomes unstable within months after it is put into a liquid solution for use by or administration to a patient.

Persons familiar with the agglomeration of crystaline particles, for use in the production of pharmaceuticals, are also generally acquainted with the fact that granulation by wet massing the materials in a mixing drum and thereafter screening and drying them has been the most common procedure. In the conventional method of wet granulation the medication (drug) is usually mixed dry with other dry ingredients. The granulating liquid can have binding agents incorporated in it (such as starch or polyvinylpyrolidone), or the liquid may have no binders at all and, instead, the liquid may dissolve a portion of the powders in the dry mix, which then acts as a binder. However, the product of wet massing can have an unpleasant odor and, due to the irregular particle size, it can have unsatisfactory dissolution properties and an unsatisfactory appearance. Furthermore, wet massing is a relatively slow process which, therefore,'is costly.

Attempts have been made to overcome these prob lems by using a fluidized bed to effect the agglomeration. For example, a machine referred to as the Fluid Bed Spray Granulator and offered by the Chemical and Pharmaceutical Industry Company, Inc. of New York, New York. has been tried for this purpose. In this type of equipment, it has heretofore been the practice to discharge the liquid coating material into the fluidized bed chamber in the form of a spray or mist. However, substantial amounts of the spray or mist are immediately entrained in the gas which activates the fluidized bed and, accordingly, quickly coat the filters in the discharge passage leading away from the fluidized bed chamber. The coated filters obstruct the outflow of gas which fluidizes the bed so that operation is promptly halted. There is no known practical or economical way of keeping the filters clean.

It was found that, by carefully controlling the manner and form of discharging the liquid into the bed, the clogging of the filters could be at least reduced to an acceptable level, if not virtually eliminated. At the same time, it was found that a more uniform particle size could be produced in the agglomeration product.

Accordingly, a primary object of this invention has been the provision of an apparatus whereby a plurality of small particles, such as granulated sugar, can be suspended in a fluidized bed and then coated with a liquid containing medication while effecting a maximum utilization of the liquid in the coating action, achieving a more uniform particle size and obtaining a far more acceptable product than is presently possible with existing procedures, such as granulation by wet massing.

A further object of this invention has been the provision of an apparatus, as aforesaid, in which a batch of agglomerated particles can be produced in a fraction of the time required by existing procedures for the same purpose, such as granulation by wet massing.

Other objects and purposes of this invention will become apparent to persons familiar with this type of equipment upon reading the following specification and examining the accompanying drawings, in which:

FIG. 1 is a side elevational view of an apparatus embodying the invention.

FIG. 2 is a sectional view taken along the line Il-II in FIG. 1.

FIG. 3 is a sectional view taken along the line llI-Ill in FIG. 2 and including sources of gas and liquid.

FIG. 4 is an enlarged sectional view taken along the line IV-IV in FIG. 2.

FIG. 5 is an enlarged sectional view taken along the line VV in FIG. 2.

FIG. 6 is an enlarged fragment of FIG. 3.

SUMMARY OF THE INVENTION The objects and purposes of the invention, including those set forth above, have been met by providing a cy lindrical, axially vertical chamber capable of providing a fluidized bed in the lower portion thereof and having a filtered gas outlet near the upper end thereof. A plurality of discharge heads are mounted within the chamber at intervals along the periphery thereof and substantially within a plane defined by the upper surface of the fluidized bed when it is operative. Each discharge head is connected to a supply of liquid containing a medication and it is arranged. sothat the liquid discharges therefrom in a stream, the initial part of which projects substantially horizontally toward the central portion of the chamber. A quantity of particles, such as granulated sugar, are suspended in the lower part of the chamber by upwardly moving gas and coated by the liquid being discharged from the heads. A gas under pressure is discharged from nozzles disposed directly above the discharge heads, said nozzles being directed so that the gas prevents a buildup of dried liquid and/or granules on the discharge ends of the heads.

DETAILED DESCRIPTION FIGS. 1, 2 and 3 illustrate an apparatus including a preferred embodiment of the invention and by means of which the process of the invention can be carried out. Said apparatus includes a central cylindrical and axially vertical housing It) which is separably connected along its lower edge to the upper edge of a conical housing ll which in turn has a porous bottom wall 12 of any conventional type capable of providing a fluidized bed. The lower end of the conical housing 11 is connected to an inlet duct 13 through which air is moved upwardly by means not shown through the porous wall I2 and thence into the chamber 14 defined within the conical housing and the lower part of the cylindrical housing. The upper end of the cylindrical housing 10 contains a plurality of filtered outlets 17 through which the gas moving up through the wall 12 can be discharged. The gas which passes upwardly through the chamber 14 may be positively forced up through the inlet duct 13, or exhausted through the filtered outlets 17, or both.

The structure of the apparatus defined thus far may be substantially conventional, the improvement being concerned with that which follows.

A pair of vertically spaced, circular conduits l8 and 19 (FIG. 3) are disposed with and near to the inside wall of the cylindrical housing 10. The upper conduit 18 (FIG. 4) is mounted upon the inner surface of the circular housing 10 near the filtered outlets 17 by means including the brackets 22. Said conduit 18 (FIG. 6) is connected by a pipe 23 to a source 24 (FIG. 2) of liquid under pressure. In this particular case, a mixture of 80% methanol and chloroform is combined with a predetermined amount of clindamycin palmitate hydrochloride to form the medicated liquid furnished by the source 24. The liquid may be pressurized by a positive displacement pump or by the application of a gas under pressure to move it from the source 24 to the conduit 18.

A plurality of tubes 26 are connected to said conduit 18, (FIG. 4) preferably at uniformly spaced intervals therealong, and each tube extends vertically downwardly near the wall of said chamber I4 from conduit 18 to a point which is preferably adjacent a plane defining the upper surface of the fluidized material when the bed is in normal operation. The lower portions 27 of the tubes 26 are curved inwardly toward the center of the chamber 14 and each lower portion 27 is connected to one end of an elongated discharge head 28 which is substantially horizontal, and extends radially inwardly toward the central portion of the chamber 14. In this particular embodiment, the inner end 31 of the discharge head 28 converges inwardly in a vertical direction and diverges outwardly in a horizontal direction. The inner face of each head 28 contains two discharge openings 32 through which the liquid discharges. More or less discharge openings may be provided as the need dictates and these openings must be of such size that, depending upon the pressure, they will produce a stream of liquid, not a mist or a spray, and this is especially important to the invention.

In this particular embodiment, there are eight discharge heads 28 which are located approximately l5 inches apart. However, other arrangements may be found suitable depending upon the type of materials and the size of the chamber 14 involved.

The lower conduit 19 (FIGS. 4 and 5) is supported by brackets 33 upon the tubes 26 near the lower ends 27 thereof. In this instance, the brackets 13 are comprised of a pair of U-bolts that extend around and engage the inner side of the conduit 19. A plate 36 is located on the outer side of the tube 26 and has openings therein through which the threaded ends of the bolts 34 extend for engagement by nuts 37. The conduit 19 is disposed on the inner sides of the tubes 26.

The conduit 19 is connected by a pipe 38 (FIG. 6) to a source 39, (FIG. 2) of gas, such as air, under pressure. A plurality of elongated nozzles 42 are connected to the conduit 19 preferably adjacent the tubes 26 and each nozzle is preferably positioned so that it extends from the conduit 19 downwardly toward the outer end of a discharge head 28 (FIG. 4). Thus, the gas discharged from the end of each nozzle 42 flows off the inner end portion of the discharge head 28 whereby to prevent the adherence or buildup of substantial amounts of dried liquid and/or particles on the end of the discharge head. That is, the principal purpose of the nozzles 42 is to keep the discharge ends of the heads 28 free from deposits of dried liquid.

A sensing head 43 (FIG. 2) is mounted upon and connected to the inner end of a pipe 44, the other end of which is connected to a detecting device 46 which is in turn connected to means (not shown) for shutting off the supply of liquid from the source 24 when the amount of certain types of vapor, such as the methanol, exceeds a predetermined percentage of the gas in the chamber 14 and thereby becomes dangerously explosive.

As shown in FIG. 6, the pipes 23, 38 and 44 extend through a sealed opening 47 in the cylindrical housing 10.

The conical housing 11 is removably connected to the cylindrical housing 10 and to the duct 13 so that said housing 11 can be disconnected from said cylindrical housing and said duct at the end of each coating operation. The housing 11 is supported by means, such as the wheeled frame 48, connected to the lower end thereof. Thus, said conical housing 11 can be moved laterally from beneath the cylindrical housing 10 for the purpose of filling it with granules or removing agglomerated particles therefrom. Inspection windows 51 and 52 are provided in the side walls of the cylindrical and conical housings, respectively, to observe the coat ing operation.

OPERATION Although the operationof the above-described apparatus will be apparent from such description to persons familiar with this type of equipment, the operation will be briefly summarized.

In normal operation of the apparatus disclosed in FIGS. 1, 2 and 3, the conical housing 11 is disconnected from the cylindrical housing 10 and the inlet duct 13 and removed laterally by means of the wheeled frame 48 so that a preselected amount of particles, such as granulated sugar, can be loaded on the bottom wall 12 of the conical housing 11. The conical housing 11 is then wheeled back into position beneath the cylindrical housing 10 and reconnected thereto as well as to the inlet duct 13. Flanges on the upper and lower ends of the conical housing 11 and on the adjoining ends of the cylindrical housing 10 and inlet duct 13 permit easy disconnection and connection of these parts.

With the conical housing 11 in place, air may be forced upwardly through or induced through the porous bottom wall 12 or both, whereby the agitated granulated sugar is suspended in a fluid bed which extends upwardly to or even slightly above the plane defined by the discharge heads 28. The liquid in source 24 (FIG. 2) is then caused to flow under pressure into the circular conduit 18 which serves as a plenum supplying all of the tubes 26, hence the heads 28 connected thereto. This liquid flows in streams through the discharge openings 32 in said heads 28, the initial part of each stream being substantially horizontal and directed toward the central portion of the chamber 14. As indicated in broken lines in FIGS. 2 and 3, the streams of liquid at least reach the central portion of the chamber 14 so that a good distribution of the liquid is achieved in the chamber 14. Normally the air moving up through the bottom wall 12 is heated substantially above the temperature of ambient air so that a more effective drying of the liquid on the granules of sugar is effected.

After a preselected period of time based upon experience with the type of materials involved, the flow of liquid from the source 24 is cut off and, after a period of time for effecting complete drying, the air flow creating the fluid bed is shut off so that the conical housing 11 can be disconnected from the cylindrical housing and theinlet duct in order to remove the batch of agglomerated particles therefrom. Using the disclosed apparatus, 200 Kgs of coated particles can be produced in less than an hour. These coated particles may be lubricated and then packaged, or they may be screened. if desired, and then lubricated and packaged.

After the batch of coated particles is removed from the conical housing 11, it is reloaded with a new batch of granulated sugar and the above-described operation is repeated.

Since the methanol used in the above-described example is highly explosive when the concentration thereof in the gas within the chamber 14 exceeds 6%, a sensing head 43 and detecting device 46 are provided to terminate the flow of liquid from the source 24 whenever the concentration of methanol in the gas within the chamber exceeds 3%. It will be recognized that these percentages will depend upon the type of materials used and the amount of precaution which is desired. In the coating operation, the methanol and chloroform act as a carrier and, in this instance, the medication acts as a binder for securing itself relatively uniformly to the granules of sugar. The use of streams of this binder rather than spray or mist thereof has been found to avoid the problem of clogged filters.

It will be recognized that other materialsmay be added to the liquid. For example, it may be desirable to add a coloring agent, an antifoaming agent, a preser vative and/or a surfactant to the clindamycin palmitate hydrochloride.

The air discharged from each nozzle 42 flows along the relatively flat upper surface and then off the discharge end of its associated head and thereby prevents the accumulation of dried liquid and/or granules on the head.

Although a particular preferred embodiment of the invention has been disclosed in detail for illustrative purposes, it will be recognized that variations or modifications of the disclosed apparatus, including the rearrangement of parts, lie within the scope of the present invention.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. In an apparatus for applying a liquid containing a binding agent, medication or other excipients to a plurality of small granules, said apparatus including a fluidized bed chamber into which ssaid granules are placed, and said chamber having an outlet for discharging the gas by which the bed is fluidized, the improvement comprising:

a source ofliquid containing a binding agent, medication or other excipients;

a plurality of discharge heads supported within said chamber and located circumferentially therearound, each discharge head including nozzle means having a substantially horizontally directed discharge opening generally facing toward the central portion of the chamber for discharging therefrom a substantially horizontal stream of liquid, said heads being located near the wall defining said chamber and substantially adjacent a horizontal plane defining the upper surface of the fluidized bed when it is operative;

first conduit means connecting said source of liquid to said heads;

pressure means for selectively urging said liquid from said source into said heads and then through said discharge openings in small streams the initial parts of which are substantially horizontal;

means for cleaning said discharge heads including a plurality of nozzles supported within said chamber and spaced circumferentially therearound, one of said nozzles being located above each discharge head and being directly downwardly away from said chamber wall and having a nozzle opening spaced upwardly from the respective discharge head to direct a stream of gas downwardly onto the upper surface of the respective discharge head; and

a source of gas under pressure and second conduit means connecting said source of gas to said nozzles whereby a stream of gas can be discharged from each nozzle onto the respective discharge head to prevent an accumulation of granules and/or liquid around the discharge opening in said discharge head.

2. An apparatus according to claim 1, wherein said chamber is substantially circular in horizontal cross section;

wherein said discharge heads are elongated and substantially radially disposed relative to said chamber; and

wherein the temperature of said gas is above ambient temperature.

3. An apparatus according to claim 1, including a sensing head disposed centrally within said chamber and spaced upwardly from said bed; and

means connected to said sensing head for detecting a predetermined percentage of a specified gas within said chamber at which the apparatus is deactivated.

4. An apparatus according to claim 2, wherein each discharge head has a horizontally elongated end portion which terminates in said discharge opening, said end portion having a tapered vertical cross-section which converges as it extends toward the discharge opening, the end portion having a tapered horizontal cross section which diverges toward the discharge opening, and the free end of said discharged head as formed on said end portion having a plurality of said discharge openings formed therein and spaced horizontally from one another.

5. An apparatus according to claim 4, wherein each of said nozzles extends inwardly and downwardly into said chamber relative to the surrounding chamber wall, said nozzle extending in a direction which forms a substantial angle with respect to both the chamber wall and the horizontally extending direction of the respective discharge head, and the nozzle opening being spaced upwardly and radially outwardly from the inner end of the discharge head for causing the stream of gas to be directed inwardly and downwardly onto the relatively flat upper surface of the respective discharge head.

6. An apparatus according to claim 1, wherein said first conduit means includes a first annular ringlike supply conduit positioned within said chamber adjacent the surrounding chamber wall, said first ringlike supply conduit being disposed substantially within a horizontal plane which is spaced upwardly a substantial distance from the horizontal plane defining the upper surface of the fluidized bed, said first ringlike supply conduit being interconnected to said source of liquid;

said first conduit means further including a plurality of intermediate conduits individually connected supply conduit being interconnected to said source of gas; and

said plurality of nozzles being fixedly interconnected to said second supply conduit at substantially uniformly spaced intervals therearound so that said nozzles are spaced substantially uniformly around said chamber adjacent said chamber wall.

7. An apparatus according to claim 6, wherein said source of gas and source of liquid are both disposed externally of said chamber, said first conduit means including a first supply pipe connected between said first supply conduit and said source of liquid, said second conduit means including a second supply pipe connected between said second supply conduit and said source of gas, and said first and second supply pipes extending through a sealed opening formed in said chamber wall. 

1. In an apparatus for applying a liquid containing a binding agent, medication or other excipients to a plurality of small granules, said apparatus including a fluidized bed chamber into which ssaid granules are placed, and said chamber having an outlet for discharging the gas by which the bed is fluidized, the improvement comprising: a source of liquid containing a binding agent, medication or other excipients; a plurality of discharge heads supported within said chamber and located circumferentially therearound, each discharge head including nozzle means having a substantially horizontally directed discharge opening generally facing toward the central portion of the chamber for discharging therefrom a substantially horizontal stream of liquid, said heads being located near the wall defining said chamber and substantially adjacent a horizontal plane defining the upper surface of the fluidized bed when it is operative; first conduit means connecting said source of liquid to said heads; pressure means for selectively urging said liquid from said source into said heads and then through said discharge openings in small streams the initial parts of which are substantially horizontal; means for cleaning said discharge heads including a plurality of nozzles supported within said chamber and spaced circumferentially therearound, one of said nozzles being located above each discharge head and being directly downwardly away from said chamber wall and having a nozzle opening spaced upwardly from the respective discharge head to direct a stream of gas downwardly onto the upper surface of the respective discharge head; and a source of gas under pressure and second conduit means connecting said source of gas to said nozzles whereby a stream of gas can be discharged from each nozzle onto the respective discharge head to prevent an accumulation of granules and/or liquid around the discharge opening in said discharge head.
 2. An apparatus according to claim 1, wherein said chamber is substantially circular in horizontal cross section; wherein said discharge heads are elongated and substantially radially disposed relative to said chamber; and wherein the temperature of said gas is above ambient temperature.
 3. An apparatus according to claim 1, including a sensing head disposed centrally within said chamber and spaced upwardly from said bed; and means connected to said sensing head for detecting a predetermined percentage of a specified gas within said chamber at which the apparatus is deactivated.
 4. An apparaTus according to claim 2, wherein each discharge head has a horizontally elongated end portion which terminates in said discharge opening, said end portion having a tapered vertical cross-section which converges as it extends toward the discharge opening, the end portion having a tapered horizontal cross section which diverges toward the discharge opening, and the free end of said discharged head as formed on said end portion having a plurality of said discharge openings formed therein and spaced horizontally from one another.
 5. An apparatus according to claim 4, wherein each of said nozzles extends inwardly and downwardly into said chamber relative to the surrounding chamber wall, said nozzle extending in a direction which forms a substantial angle with respect to both the chamber wall and the horizontally extending direction of the respective discharge head, and the nozzle opening being spaced upwardly and radially outwardly from the inner end of the discharge head for causing the stream of gas to be directed inwardly and downwardly onto the relatively flat upper surface of the respective discharge head.
 6. An apparatus according to claim 1, wherein said first conduit means includes a first annular ringlike supply conduit positioned within said chamber adjacent the surrounding chamber wall, said first ringlike supply conduit being disposed substantially within a horizontal plane which is spaced upwardly a substantial distance from the horizontal plane defining the upper surface of the fluidized bed, said first ringlike supply conduit being interconnected to said source of liquid; said first conduit means further including a plurality of intermediate conduits individually connected between the respective discharge heads and said first ringlike supply conduit, said intermediate conduits extending downwardly in said chamber adjacent the surrounding chamber wall; said second conduit means including a second annular ringlike supply conduit positioned within said chamber adjacent the chamber wall, said second supply conduit being disposed substantially within a horizontal plane which is spaced upwardly a substantial distance from the horizontal plane defining the upper surface of the fluidized bed, said second supply conduit being interconnected to said source of gas; and said plurality of nozzles being fixedly interconnected to said second supply conduit at substantially uniformly spaced intervals therearound so that said nozzles are spaced substantially uniformly around said chamber adjacent said chamber wall.
 7. An apparatus according to claim 6, wherein said source of gas and source of liquid are both disposed externally of said chamber, said first conduit means including a first supply pipe connected between said first supply conduit and said source of liquid, said second conduit means including a second supply pipe connected between said second supply conduit and said source of gas, and said first and second supply pipes extending through a sealed opening formed in said chamber wall. 